RESUMEN
Phytochemical analysis of Chloranthus henryi var. hupehensis roots led to the identification of a new eudesmane sesquiterpenoid dimer, 18 new sesquiterpenoids, and three known sesquiterpenoids. Among the isolates, 1 was a rare sesquiterpenoid dimer that is assembled by a unique oxygen bridge (C11-O-C8') of two highly rearranged eudesmane-type sesquiterpenes with the undescribed C16 carbon framework. (+)-2 and (-)-2 were a pair of new skeleton dinorsesquiterpenoids with a remarkable 6/6/5 tricyclic ring framework including one γ-lactone ring and the bicyclo[3.3.1]nonane core. Their structures were elucidated using spectroscopic data, single-crystal X-ray diffraction analysis, and quantum chemical computations. In the LPS-induced BV-2 microglial cell model, 17 suppressed IL-1ß and TNF-α expression with EC50 values of 6.81 and 2.76 µM, respectively, indicating its excellent efficacy in inhibiting inflammatory factors production in a dose dependent manner and without cytotoxicity. In subsequent mechanism studies, compounds 3, 16, and 17 could reduce IL-1ß and TNF-α production by inhibiting IKBα/p65 pathway activation.
Asunto(s)
Relación Dosis-Respuesta a Droga , Raíces de Plantas , Sesquiterpenos , Transducción de Señal , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Raíces de Plantas/química , Transducción de Señal/efectos de los fármacos , Estructura Molecular , Ratones , Animales , Relación Estructura-Actividad , Factor de Transcripción ReIA/metabolismo , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Descubrimiento de Drogas , Inhibidor NF-kappaB alfa/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificaciónRESUMEN
In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 µM. Moreover, 1, 2, and 5 significantly decreased both the mRNA and protein levels of the target SREBP-1c, and 5 also reduced PPARα mRNA and protein levels. Therefore, 1, 2, and 5 are potential drugs against hepatic steatosis by targeting PPARα or SREBP-1c.
Asunto(s)
Bibencilos , Dendrobium , Hígado Graso , Bibencilos/farmacología , Bibencilos/química , Dendrobium/química , PPAR alfa , ARN Mensajero , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Naftalenos/química , Naftalenos/farmacologíaRESUMEN
(+)- and (-)-Chlorahupetenes A (1a and 1b), B (2a and 2b), C (3a and 3b), and D (4a and 4b), four unique enantiomeric pairs of eudesmane-type sesquiterpenoid dimers with two new carbon skeletons, were isolated from the aerial parts of Chloranthus henryi var. hupehensis. Compounds 1 and 2 possess an unprecedented 6/6/5/6/6 pentacyclic carbon skeleton with a new dimerization pattern of two eudesmane-type sesquiterpenoids. Compounds 3 and 4, which are fused with two eudesmane-type sesquiterpenoids via an unprecedented five-membered O-heterocyclic ring, represent a new 6/6/5/5/6/6/5 heptacyclic ring system. The structures of the compounds were determined through spectroscopic data and X-ray crystallography. Compounds 1a-3b significantly inhibited NO production with IC50 values ranging from 9.62 to 12.91 µM. Moreover, compounds 1b and 3a suppressed the production of a proinflammatory mediator (TNF-α) and enzyme expression (iNOS) at the mRNA level.